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- W2908873386 abstract "Background Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are known to play an important role in immune response regulation via a co-inhibitory signal during T cell activation. Genome-wide association studies in humans and the fact that PD-1 knock-out mice develop a lupus-like pathology point toward the involvement of the PD-1 pathway in the pathogenesis of systemic lupus erythematosus (SLE).1 2 However, little is known regarding the role of this pathway in B cells from patients with SLE. Objectives This study addressed the kinetics of PD-1, PD-L1 and PD-L2 expression on B cells from patients with SLE. Methods Blood samples were obtained from healthy donors (HD) and SLE patients. PBMCs from HD and SLE patients were stimulated with IL2/IL10, aBCR (IgG/IgM/IgA), CpG oligodeoxynucleotides (CpG) and CD40L alone or in combination. The membrane expression of PD-1, PD-L1 and PD-L2 on CD19 +CD20+B cells was measured by FACS at baseline and after 48 hour stimulation. Results At baseline, the expression of PD-1, PD-L1 and PD-L2 on B cells between HD and SLE patients was similar. Notably, 48 hour stimulation of B cells with IL2/IL10, aBCR, CpG and CD40L gave rise to twofold reduced expression of PD-L1 by SLE compared to HD B cells. Interestingly, PD-L1 expression by SLE B cells was increased only in presence of CD40L, whereas in HD the mix of CpG, aBCR, and IL2/IL10 led also to a significant increase in PD-L1 expression. Conclusions The data suggest that activation of B cells from SLE patients require CD40/CD40L interaction to increase PD-L1 expression, which is, however, reduced compared to HD. Diminished PD-L1 expression upon B cell stimulation is consistent with impaired inhibition of T cells in SLE (figure 1). References [1] Nishimura H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity1999;11(2):141–151. [2] Prokunina L, et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet2002;32(4):666–9. Disclosure of Interest None declared" @default.
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- W2908873386 date "2018-06-01" @default.
- W2908873386 modified "2023-10-02" @default.
- W2908873386 title "AB0150 Diminished expression of pd-l1 by activated b cells is characteristic of sle" @default.
- W2908873386 doi "https://doi.org/10.1136/annrheumdis-2018-eular.2716" @default.
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